Effect of Ginkgo biloba extract on oxidative metabolism of valproic acid in hepatic microsomes from donors with the CYP2C9*1/*1 genotypeThis article is one of a selection of papers published in this special issue (part 1 of 2) on the Safety and Efficacy of Natural Health Products.

2007 ◽  
Vol 85 (9) ◽  
pp. 848-855 ◽  
Author(s):  
Andrew M. Numa ◽  
Frank S. Abbott ◽  
Thomas K.H. Chang

We investigated the effect of Ginkgo biloba extracts and some of its individual constituents on the oxidative metabolism of valproic acid (VPA) in hepatic microsomes from donors with the CYP2C9*1/*1 genotype. G. biloba extract decreased 4-ene-VPA, 3-OH-VPA, 4-OH-VPA, and 5-OH-VPA formation with mean (± SE) IC50 values of 340 ± 40 μg/mL, 370 ± 100 μg/mL, 180 ± 30 μg/mL, and 210 ± 20 μg/mL, respectively. This was associated with inhibition of not only CYP2C9*1, but also CYP2A6 and CYP2B6. Bilobalide, ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, quercetin-3-O-rutinoside, kaempferol-3-O-rutinoside, and isorhamnetin-3-O-rutinoside were not responsible for the inhibition of VPA metabolism by the extract. When analyzed as the sum of the aglycone and total glycosides present in the extract, quercetin decreased 4-ene-VPA, 4-OH-VPA, and 5-OH-VPA formation by 76%, 51%, and 70%, respectively, kaempferol decreased 4-ene-VPA, 4-OH-VPA, and 5-OH-VPA formation by 65%, 46%, and 49%, respectively, and isorhamnetin decreased 4-ene-VPA, 4-OH-VPA, and 5-OH-VPA formation by 29%, 26%, and 31%, respectively. The 3 aglycones did not affect 3-OH-VPA formation. In summary, G. biloba extract decreased hepatic microsomal formation of 4-ene-VPA, 4-OH-VPA, 5-OH-VPA, and 3-OH-VPA, but the effect was not due to the terpene trilactones or flavonol glycosides investigated in our study.

2005 ◽  
Vol 88 (1) ◽  
pp. 26-29 ◽  
Author(s):  
Guillaume A Lawrence ◽  
Peter M Scott

Abstract A simple extraction procedure was applied to the analysis of canned/packaged white nuts and Ginkgo biloba extracts. Extraction by shaking with water at room temperature was more convenient to use than a previously published Soxhlet procedure for analysis of packaged Ginkgo biloba seeds (white nuts) for ginkgotoxin; recoveries from spiked dried seeds by the simple extraction procedure averaged 76%. Determination was by liquid chromatography with UV or fluorescence detection. Recoveries of ginkgotoxin from a spiked and unspiked natural health product (powder from Ginkgo biloba capsules) were equivalent by both procedures; recovery from spiked powder by the simple extraction procedure was 81%. Application of this extraction procedure in the analysis of 6 samples of white nuts (vacuum packaged and canned products) showed that free ginkgotoxin was present in 5 samples at concentrations up to 25 μg/g dry weight. Total ginkgotoxin was determined after hydrolysis with β-glucosidase of sample extracts in which a peak corresponding to the 5′-O-glucoside was detected. Ginkgotoxin was determined in 10 Ginkgo biloba natural health products by the same method at levels up to 181 μg/g.


2004 ◽  
Vol 82 (1) ◽  
pp. 57-64 ◽  
Author(s):  
I fan Kuo ◽  
Jie Chen ◽  
Thomas K.H Chang

The present study investigated the in vitro effect of Ginkgo biloba extracts and some of the individual constituents (ginkgolides, bilobalide, and flavonols such as kaempferol, quercetin, isorhamnetin, and their glycosides) on CYP1A-mediated 7-ethoxyresorufin O-dealkylation in hepatic microsomes isolated from rats induced with β-naphthoflavone. G. biloba extract competitively inhibited CYP1A activity, with an apparent Ki value of 1.6 ± 0.4 µg/mL (mean ± SE). At the concentrations present in the G. biloba extracts, ginkgolides A, B, C, and J and bilobalide did not affect CYP1A activity, whereas kaempferol (IC50 = 0.006 ± 0.001 µg/mL, mean ± SE), isorhamnetin (0.007 ± 0.001 µg/mL), and quercetin (0.050 ± 0.003 µg/mL) decreased this activity. The monoglycosides (1 and 10 µg/mL) and diglycosides (10 µg/mL) of kaempferol and quercetin but not those of isorhamnetin also inhibited CYP1A activity. The order of inhibitory potency was kaempferol ~ isorhamnetin > quercetin, and for each of these flavonols the order of potency was aglycone >> monoglycoside > diglycoside. In summary, G. biloba extract competitively inhibited rat hepatic microsomal CYP1A activity, but the effect was not due to ginkgolides A, B, C, or J, bilobalide, kaempferol, quercetin, isorhamnetin, or the respective flavonol monoglycosides or diglycosides.Key words: bilobalide, CYP1A, cytochrome P450, Ginkgo biloba, ginkgolide, flavonol.


2020 ◽  
Vol 16 (7) ◽  
pp. 893-904
Author(s):  
Alessandra von Ahn ◽  
João Henrique Z. dos Santos

Background: The official compendium of the quantification of ginkgo flavonoids from Ginkgo biloba extract has been proposed using HPLC. The drawbacks of this technique appear to be due to the restricted efficiency in terms of the recovery results and suitability of the system for the quantification of these compounds. This study investigated the potential advantages and limitations of the development of efficient extraction methods for the recovery of flavonol glycosides (quercetin, kaempferol and isorhamnetin) and terpene trilactones (bilobalide, ginkgolide A, ginkgolide B and ginkgolide C) using extraction, quantification and detection techniques, namely, GC-FID and UHPLC-DAD, which are alternatives to those techniques available in the literature. Methods: Two different extraction methodologies have been developed for the determination of flavonoids (quercetin, kaempferol and isorhamnetin) and terpene trilactones (bilobalide, ginkgolide A, ginkgolide B and ginkgolide C) using ultra-high-pressure liquid chromatography coupled to a diode array detector and gas chromatography coupled to a flame ionization detector. Results: In this study, the Ginkgo biloba extract mass, hydrolysis preparation method (with or without reflux), and volume of the extraction solution seemed to affect the ginkgo flavonoid recovery. The UHPLC-based method exhibited higher extraction efficiency for ginkgo flavonoid quantification compared to the pharmacopoeial method. The developed method exhibited higher extraction efficiency for terpene quantification compared to the previous method that used extractive solution without pH adjustment, with less time of extraction and less amount of the sample and organic solvent aliquots. Conclusion: The UHPLC and GC analysis methods established in this study are both effective and efficient. These methods may improve the quality control procedures for ginkgo extract and commercial products available in today´s natural health product market. The results indicate that redeveloped extraction methods can be a viable alternative to traditional extraction methods.


2021 ◽  
Vol 20 ◽  
pp. 153473542199007
Author(s):  
Siddhartha Sood ◽  
Rahul Jayachandiran ◽  
Siyaram Pandey

Melanoma is the deadliest form of skin cancer in the world with a growing incidence in North America. Contemporary treatments for melanoma include surgical resection, chemotherapy, and radiotherapy. However, apart from resection in early melanoma, the prognosis of patients using these treatments is typically poor. In the past decade, there have been significant advancements in melanoma therapies. Immunotherapies such as ipilimumab and targeted therapies such as vemurafenib have emerged as a promising option for patients as seen in both scientific and clinical research. Furthermore, combination therapies are starting to be administered in the form of polychemotherapy, polyimmunotherapy, and biochemotherapy, of which some have shown promising outcomes in relative efficacy and safety due to their multiple targets. Alongside these treatments, new research has been conducted into the evidence-based use of natural health products (NHPs) and natural compounds (NCs) on melanoma which may provide a long-term and non-toxic form of complementary therapy. Nevertheless, there is a limited consolidation of the research conducted in emerging melanoma treatments which may be useful for researchers and clinicians. Thus, this review attempts to evaluate the therapeutic efficacy of current advancements in metastatic melanoma treatment by surveying new research into the molecular and cellular basis of treatments along with their clinical efficacy. In addition, this review aims to elucidate novel strategies that are currently being used and have the potential to be used in the future.


2004 ◽  
Vol 38 (9) ◽  
pp. 1406-1411 ◽  
Author(s):  
Mário L de Lemos ◽  
Leela John ◽  
Lynne Nakashima ◽  
Robin K O'Brien ◽  
Suzanne CM Taylor

2011 ◽  
Vol 13 (1) ◽  
pp. 102 ◽  
Author(s):  
Sarah Khalifé ◽  
Muhammad Zafarullah

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